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Scientific Reports Jun 2024Transforming growth factor β (TGF-β) is implicated in both mesothelial-to-mesenchymal transition (MMT) and cellular senescence of human peritoneal mesothelial cells...
Transforming growth factor β (TGF-β) is implicated in both mesothelial-to-mesenchymal transition (MMT) and cellular senescence of human peritoneal mesothelial cells (HPMCs). We previously showed that senescent HPMCs could spontaneously acquire some phenotypic features of MMT, which in young HPMCs were induced by TGF-β. Here, we used electron microscopy, as well as global gene and protein profiling to assess in detail how exposure to TGF-β impacts on young and senescent HPMCs in vitro. We found that TGF-β induced structural changes consistent with MMT in young, but not in senescent HPMCs. Of all genes and proteins identified reliably in HPMCs across all treatments and states, 4,656 targets represented overlapping genes and proteins. Following exposure to TGF-β, 137 proteins and 46 transcripts were significantly changed in young cells, compared to 225 proteins and only 2 transcripts in senescent cells. Identified differences between young and senescent HPMCs were related predominantly to wound healing, integrin-mediated signalling, production of proteases and extracellular matrix components, and cytoskeleton structure. Thus, the response of senescent HPMCs to TGF-β differs or is less pronounced compared to young cells. As a result, the character and magnitude of the postulated contribution of HPMCs to TGF-β-induced peritoneal remodelling may change with cell senescence.
Topics: Humans; Cellular Senescence; Transforming Growth Factor beta; Epithelial Cells; Peritoneum; Epithelial-Mesenchymal Transition; Cells, Cultured; Epithelium; Signal Transduction; Gene Expression Profiling
PubMed: 38830931
DOI: 10.1038/s41598-024-63250-1 -
AME Medical Journal Jun 2023Pancreatic cancer is the fourth most common cause of cancer-related death in the United States. Despite advancements in surgery and chemoradiation therapies, pancreatic...
BACKGROUND
Pancreatic cancer is the fourth most common cause of cancer-related death in the United States. Despite advancements in surgery and chemoradiation therapies, pancreatic cancer has a 5-year survival rate of only 11% in the United States. Cryoablation is emerging as a new and effective therapy for locally advanced pancreatic cancer and symptom palliation in metastatic disease. To our knowledge, the occurrence of disseminated intravascular coagulation (DIC) after cryoablation is rare.
CASE DESCRIPTION
A 47-year-old woman with no significant past medical history was diagnosed with pancreatic cancer and underwent a Whipple procedure followed by chemotherapy with gemcitabine and paclitaxel. Due to the abdominal lymph nodes, peritoneum, right femur, and surrounding soft tissue metastases, she received systemic palliative chemotherapy with gemcitabine and paclitaxel and underwent right femur tumor excision, open reduction, and internal fixation, followed by radiation therapy. She continued to have persistent pain and underwent palliative percutaneous cryoablation of the metastatic tumor under computed tomography (CT) and ultrasound guidance. Immediately post procedure, she developed slow but continuous blood oozing at the ablation site, which was difficult to control despite compression dressings, reinforcement sutures, and local thrombin powder. The patient was transferred to the intensive care unit where she was noted to be hypotensive and tachycardic, with petechiae in both lower extremities. Laboratory studies were consistent with DIC and peripheral blood smear revealed multiple schistocytes. CT angiogram of the right lower extremity did not show any bleeding vessel amenable to embolization. She was transfused red blood cells, platelets, fresh frozen plasma, and cryoprecipitate. Despite multiple daily transfusions, she continued to have pain and remained persistently thrombocytopenic and coagulopathic. After discussion with the patient and her family, she chose to transition to comfort care measures and died.
CONCLUSIONS
DIC is an unusual but life-threatening complication of advanced pancreatic cancer.
PubMed: 38827122
DOI: 10.21037/amj-23-13 -
Cureus May 2024Metastasis of gastric carcinoma to atypical locations can complicate management, often leading clinicians to rely heavily on chemotherapy. While instances of gastric...
Metastasis of gastric carcinoma to atypical locations can complicate management, often leading clinicians to rely heavily on chemotherapy. While instances of gastric carcinoma spreading to the liver, peritoneum, and lymphatics are well documented in the literature, there is limited evidence of its spread to intraintestinal organs, particularly the colon. This scarcity of reports complicates diagnosis, given the variations in histopathology. This case report highlights a 35-year-old patient diagnosed with colonic metastasis from hereditary diffuse gastric cancer (HDGC) while being evaluated for potential causes of iron deficiency anemia. A mutation in the E-cadherin (CDH1) tumor suppressor gene is associated with HDGC. Dysregulation of CDH1 leads to tumor proliferation, invasion, migration, and metastasis. Treatment options for gastric cancer include surgical resection with neoadjuvant or adjuvant chemotherapy or palliative care with chemotherapy in metastatic disease. Although colonic metastasis from gastric cancer is rare, documented incidents can offer valuable insights that avoid misdiagnosing primary tumors and help guide further management.
PubMed: 38826894
DOI: 10.7759/cureus.59483 -
World Journal of Gastrointestinal... May 2024Neuroendocrine carcinoma (NEC) of the extrahepatic bile duct is very rare, and the treatment and prognosis are unclear. Herein, we report the case of a middle-aged...
BACKGROUND
Neuroendocrine carcinoma (NEC) of the extrahepatic bile duct is very rare, and the treatment and prognosis are unclear. Herein, we report the case of a middle-aged female with primary large cell NEC (LCNEC) of the common hepatic duct combined with distal cholangiocarcinoma (dCCA). Additionally, after a review of the relevant literature, we summarize and compare mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) and pure NEC to provide a reference for selecting the appropriate treatment and predicting the prognosis of this rare disease.
CASE SUMMARY
A 62-year-old female presented to the hospital due to recurrent abdominal pain for 2 months. Physical examination showed mild tenderness in the upper abdomen and a positive Courvoisier sign. Blood tests showed elevated liver transaminase and carbohydrate antigen 199 levels. Imaging examination revealed a 1-cm tumour in the middle and lower segments of the common bile duct. Pancreaticoduodenectomy + lymph node dissection was performed, and hepatic duct tumours were unexpectedly found during surgery. Pathology suggested poorly differentiated LCNEC (approximately 0.5 cm × 0.5 cm × 0.4 cm), Ki-67 (50%), synaptophysin+, and chromogranin A+. dCCA pathology suggested moderately differentiated adenocarcinoma. The patient eventually developed lymph node metastasis in the liver, bone, peritoneum, and abdominal cavity and died 24 months after surgery. Gene sequencing methods were used to compare gene mutations in the two primary bile duct tumours.
CONCLUSION
The prognosis of MiNEN and pure NEC alone is different, and the selection of treatment options needs to be differentiated.
PubMed: 38817298
DOI: 10.4240/wjgs.v16.i5.1449 -
Annals of Pediatric Cardiology 2023Pentalogy of Cantrell is a rare congenital anomaly involving the anterior diaphragm, pericardium, sternum, peritoneum, and associated intracardiac defects. In this...
Pentalogy of Cantrell is a rare congenital anomaly involving the anterior diaphragm, pericardium, sternum, peritoneum, and associated intracardiac defects. In this report, we describe a neonate with pentalogy of Cantrell evaluated with multimodality imaging and successfully managed by a multidisciplinary team.
PubMed: 38817252
DOI: 10.4103/apc.apc_188_23 -
The Medical Journal of Malaysia May 2024The complete mesocolic excision (CME) and central vascular ligation (CVL) is an advanced surgical technique used to treat colon cancer. It combines the removal of the... (Comparative Study)
Comparative Study
INTRODUCTION
The complete mesocolic excision (CME) and central vascular ligation (CVL) is an advanced surgical technique used to treat colon cancer. It combines the removal of the affected portion of the colon and surrounding lymph nodes with an improved method of controlling the vascular supply to the tumour.
MATERIALS AND METHODS
A retrospective study of patients with colon cancer underwent right hemicolectomy (either CME and CVL or conventional method) were operated by colorectal surgeons in a tertiary centre in Kuala Lumpur from 2018 to 2020. We review the data to compare the oncological, pathological and surgical outcomes of both techniques. Categorical variables were presented as frequencies and percentages. Continuous variables were compared using an independent t-test or Mann-Whitney Rank U test. The chi-square test was used to determine the association between categorical variables and mortality. Statistical analysis was conducted with IBM SPSS Statistics 25.0, and statistical significance was set at p<0.05.
RESULTS
A total of 30 patients (CME and CVL=15 or conventional colectomies=15) were included in this study with mean age of 65 years. There was no statistical difference between the mean age of the two groups (p=0.355). Most of the patients were Malays (46.7%) followed by Chinese (43.3 %) and Indians (10.0%). The mean (SD) = 19 (9) number of lymph nodes harvested is more in CME and CVL groups which however is not statistically significant compared to the mean (SD) = 16 (9), number of lymph nodes in conventional colectomies. The duration of surgery is longer in CME and CVL groups (214 minutes) compared to conventional colectomies (188 minutes) but with no significant statistical difference. Most of the perioperative complications were similar in both groups with no significant statistical differences.
CONCLUSION
CME and CVL are not inferior to conventional surgery in colon surgery in a tertiary centre. It should be considered since the advantages such as lymph node yield and median recurrence free survival are better with similar perioperative morbidity.
Topics: Humans; Colonic Neoplasms; Retrospective Studies; Male; Female; Ligation; Aged; Colectomy; Mesocolon; Middle Aged; Tertiary Care Centers; Malaysia; Treatment Outcome
PubMed: 38817066
DOI: No ID Found -
Breast Cancer Research : BCR May 2024Despite progress understanding the mechanisms underlying tumor spread, metastasis remains a clinical challenge. We identified the choline-producing...
BACKGROUND
Despite progress understanding the mechanisms underlying tumor spread, metastasis remains a clinical challenge. We identified the choline-producing glycerophosphodiesterase, EDI3 and reported its association with metastasis-free survival in endometrial cancer. We also observed that silencing EDI3 slowed cell migration and other cancer-relevant phenotypes in vitro. Recent work demonstrated high EDI3 expression in ER-HER2+ breast cancer compared to the other molecular subtypes. Silencing EDI3 in ER-HER2+ cells significantly reduced cell survival in vitro and decreased tumor growth in vivo. However, a role for EDI3 in tumor metastasis in this breast cancer subtype was not explored. Therefore, in the present work we investigate whether silencing EDI3 in ER-HER2+ breast cancer cell lines alters phenotypes linked to metastasis in vitro, and metastasis formation in vivo using mouse models of experimental metastasis.
METHODS
To inducibly silence EDI3, luciferase-expressing HCC1954 cells were transduced with lentiviral particles containing shRNA oligos targeting EDI3 under the control of doxycycline. The effect on cell migration, adhesion, colony formation and anoikis was determined in vitro, and significant findings were confirmed in a second ER-HER2+ cell line, SUM190PT. Doxycycline-induced HCC1954-luc shEDI3 cells were injected into the tail vein or peritoneum of immunodeficient mice to generate lung and peritoneal metastases, respectively and monitored using non-invasive bioluminescence imaging. Metabolite levels in cells and tumor tissue were analyzed using targeted mass spectrometry and MALDI mass spectrometry imaging (MALDI-MSI), respectively.
RESULTS
Inducibly silencing EDI3 reduced cell adhesion and colony formation, as well as increased susceptibility to anoikis in HCC1954-luc cells, which was confirmed in SUM190PT cells. No influence on cell migration was observed. Reduced luminescence was seen in lungs and peritoneum of mice injected with cells expressing less EDI3 after tail vein and intraperitoneal injection, respectively, indicative of reduced metastasis. Importantly, mice injected with EDI3-silenced cells survived longer. Closer analysis of the peritoneal organs revealed that silencing EDI3 had no effect on metastatic organotropism but instead reduced metastatic burden. Finally, metabolic analyses revealed significant changes in choline and glycerophospholipid metabolites in cells and in pancreatic metastases in vivo.
CONCLUSIONS
Reduced metastasis upon silencing supports EDI3's potential as a treatment target in metastasizing ER-HER2+ breast cancer.
Topics: Animals; Female; Humans; Mice; Cell Line, Tumor; Receptor, ErbB-2; Breast Neoplasms; Receptors, Estrogen; Disease Models, Animal; Cell Movement; Gene Knockdown Techniques; Tumor Burden; Neoplasm Metastasis; Lung Neoplasms; Cell Proliferation
PubMed: 38816770
DOI: 10.1186/s13058-024-01849-y -
EClinicalMedicine Jun 2024Caesarean section (CS) is the most performed major surgery worldwide. Surgical techniques used for CS vary widely and there is no internationally accepted... (Review)
Review
BACKGROUND
Caesarean section (CS) is the most performed major surgery worldwide. Surgical techniques used for CS vary widely and there is no internationally accepted standardization. We conducted an overview of systematic reviews (SR) of randomized controlled trials (RCT) to summarize the evidence on surgical techniques or procedures related to CS.
METHODS
Searches were conducted from database inception to 31 January 2024 in Cochrane Database of Systematic Reviews, PubMed, EMBASE, Lilacs and CINAHL without date or language restrictions. AMSTAR 2 and GRADE were used to assess the methodological quality of the SRs and the certainty of evidence at outcome level, respectively. We classified each procedure-outcome pair into one of eight categories according to effect estimates and certainty of evidence. The overview was registered at PROSPERO (CRD 42023208306).
FINDINGS
The analysis included 38 SRs (16 Cochrane and 22 non-Cochrane) published between 2004-2024 involving 628 RCT with a total of 190,349 participants. Most reviews were of low or critically low quality (AMSTAR 2). The SRs presented 345 procedure-outcome comparisons (237 procedure versus procedure, 108 procedure versus no treatment/placebo). There was insufficient or inconclusive evidence for 256 comparisons, clear evidence of benefit for 40, possible benefit for 17, no difference of effect for 13, clear evidence of harm for 14, and possible harm for 5. We found no SRs for 7 pre-defined procedures. Skin cleansing with chlorhexidine, Joel-Cohen-based abdominal incision, uterine incision with blunt dissection and cephalad-caudal expansion, cord traction for placental extraction, manual cervical dilatation in pre-labour CS, changing gloves, chromic catgut suture for uterine closure, non-closure of the peritoneum, closure of subcutaneous tissue, and negative pressure wound therapy are procedures associated with benefits for relevant outcomes.
INTERPRETATION
Current evidence suggests that several CS surgical procedures improve outcomes but also reveals a lack of or inconclusive evidence for many commonly used procedures. There is an urgent need for evidence-based guidelines standardizing techniques for CS, and trials to fill existing knowledge gaps.
FUNDING
UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored programme executed by the World Health Organization (WHO).
PubMed: 38812964
DOI: 10.1016/j.eclinm.2024.102632 -
Frontiers in Veterinary Science 2024This report describes a case of transmural migration of a gossypiboma from the peritoneum into the urinary bladder in a 4-year-old, female spayed, mixed-breed dog. The...
This report describes a case of transmural migration of a gossypiboma from the peritoneum into the urinary bladder in a 4-year-old, female spayed, mixed-breed dog. The dog was presented on an emergency basis for complete urethral obstruction with radiographic evidence of urocystolithiasis. An exploratory laparotomy was performed and a 4-5 cm mass was identified which was confluent with the apex of the urinary bladder. The mass and bladder were exteriorized and isolated, and an apical, partial cystectomy was performed to remove the mass and gain access to the uroliths within the lumen of the bladder. A 4×4 surgical sponge was identified within the trigone of the bladder, it had multiple uroliths; another sponge was also found within the mass itself. This case demonstrates an atypical cause of urethral obstruction and serves as the first reported case of transmural migration of a gossypiboma into the urinary bladder of a dog. It also illustrates the importance of establishing routine operating procedures including gauze counts and the use of radiopaque-labeled surgical gauze.
PubMed: 38812558
DOI: 10.3389/fvets.2024.1394052 -
Cell Death & Disease May 2024Epithelial-to-mesenchymal transition (EMT) is one of the main causes of peritoneal fibrosis. However, the pathophysiological mechanisms of EMT, specifically its...
Epithelial-to-mesenchymal transition (EMT) is one of the main causes of peritoneal fibrosis. However, the pathophysiological mechanisms of EMT, specifically its relationship with autophagy, are still unknown. This study aimed to evaluate the role of autophagy in transforming growth factor-beta 1 (TGF-β1)-induced EMT in human peritoneal mesothelial cells (HPMCs). Primary cultured HPMCs were treated with TGF-β1 (2 and 5 ng/mL) and changes in autophagy markers and the relationship between autophagy and EMT were evaluated. We also identified changes in EMT- and autophagy-related signaling pathways after autophagy and NADPH oxidase 4 (NOX4) inhibition. TGF-β1 increased the generation of NOX4 and reactive oxygen species (ROS) in HPMCs, resulting in mitochondrial damage. Treatment with GKT137831 (20 μM), a NOX1/4 inhibitor, reduced ROS in the mitochondria of HPMC cells and reduced TGF-β1-induced mitochondrial damage. Additionally, the indirect inhibition of autophagy by GKT137831 (20 μM) downregulated TGF-β1-induced EMT, whereas direct inhibition of autophagy using 3-methyladenine (3-MA) (2 mM) or autophagy-related gene 5 (ATG5) gene silencing decreased the TGF-β1-induced EMT in HPMCs. The suppressor of mothers against decapentaplegic 2/3 (Smad2/3), autophagy-related phosphoinositide 3-kinase (PI3K) class III, and protein kinase B (Akt) pathways, and mitogen-activated protein kinase (MAPK) signaling pathways, such as extracellular signal-regulated kinase (ERK) and P38, were involved in TGF-β1-induced EMT. Autophagy and NOX4 inhibition suppressed the activation of these signaling pathways. Direct inhibition of autophagy and its indirect inhibition through the reduction of mitochondrial damage by upstream NOX4 inhibition reduced EMT in HPMCs. These results suggest that autophagy could serve as a therapeutic target for the prevention of peritoneal fibrosis in patients undergoing peritoneal dialysis.
Topics: Humans; Epithelial-Mesenchymal Transition; Transforming Growth Factor beta1; Autophagy; Oxidative Stress; Reactive Oxygen Species; NADPH Oxidase 4; Signal Transduction; Epithelial Cells; Mitochondria; Peritoneum; Pyrazolones; Pyridones
PubMed: 38806451
DOI: 10.1038/s41419-024-06753-z